Clinical Research Directory

Prevalence of NAFLD and Advanced Fibrosis in Patients With Type 1 Diabetes

The aim of this study is to assess the prevalence of nonalcoholic fatty liver disease (NAFLD) in patients with type 1 diabetes receiving care at Joslin clinic using noninvasive imaging and serum-based methods with the goal of identifying high-risk patients with advanced fibrosis who should be prioritized for specialty referral

Prophylactic Antibiotics in Endoscopic Secondary Prevention of Gastroesophageal Variceal Bleeding

Whether prophylactic antibiotics should be administered in the endoscopic secondary prevention of GVB or not is unclear. In this non-inferiority trial, we are aimed to evaluate whether prophylactic antibiotics are essential in the endoscopic secondary prevention of cirrhotic patients with gastroesophageal variceal bleeding.

Testing LiverWatch, a Home-Based Remote-Monitoring Intervention for Advanced Liver Disease

Remote healthcare monitoring for cirrhosis has shown promise in overcoming barriers to accessing specialty care, improving healthcare quality, and reducing mortality. The LiverWatch study is investigating whether a remote nutrition, physical activity, and education intervention can improve health outcomes in those with cirrhosis. In this clinical trial, individuals will be randomized to either enhanced usual care or the LiverWatch intervention. Both groups are given fitbits and asked to increase their step counts. Those in the Liverwatch group will be incentivized for increase their physical activity while also undergoing a personalized nutrition intervention and weekly symptom monitoring and cirrhosis education.

Evidence Based Mental Wellness Programming Online for Adults Across Chronic Physical Conditions

Chronic physical conditions are defined as conditions that require ongoing management and treatment over extended periods of time. Chronic physical conditions are not only leading causes of death and disability in North America but they are commonly associated with mental distress and reduced quality of life. Online mind-body wellness programming ranging from physical activity to mindfulness interventions has been shown to be effective in improving mental wellness in a variety of chronic disease populations, but there is a need to evaluate scalable ways to deliver these programs. Building upon a previously developed online wellness program for inflammatory bowel disease (IBD) and primary biliary cholangitis (PBC), the research team has developed a mind-body wellness program for adults ≥18 years of age living with different chronic conditions (e.g., cirrhosis, PBC, heart failure). The 12-week program will be delivered online, and include follow- along mindful movement, breathwork and meditation routines, and a psychology based coping skills program. In a three-armed randomized controlled trial, the study will assess the impact on the primary outcome of anxiety and depression as measured through the hospital anxiety and depression scale (HADS). At the beginning and the end of the 12-week research study, participants will complete surveys to assess secondary/exploratory outcome measures including quality of life, fatigue, frailty, demoralization, and healthcare usage. After the program, the research team will conduct interviews with participants to allow them to share their other feedback about the program. The researchers will also send surveys to the participants eight weeks after the program ends to assess longer- term impacts on primary and secondary outcomes.

Changes in Glucose Tolerance in Patients With Cirrhosis Peri-Liver Transplant

The goal of this observational study is to establish risk factors for post-transplant in adult individuals with cirrhosis without diabetes undergoing liver transplant evaluation. The question being addressed is: can laboratory work, anthropometric tests, functional tests, imaging, and advanced measurements such as wrist actigraphy, continuous glucose monitoring, or oral glucose tolerance testing predict the development of diabetes after liver transplant? Participants will be asked to periodically participate in wearing a continuous glucose monitor and wrist actigraph and obtain an oral glucose tolerance test both before and after liver transplant.

4beta-hydroxycholesterol in Cirrhosis

The aim is to evaluate the levels of oxysterols and especially 4beta-hydroxycholesterol in patients with liver cirrhosis. Three cirrhosis cohorts are recruited: patients treated with spironolactone, patients treated with rifaximin, patients without spironolactone or rifaximin. Also three other control cohorts are recruited: patients with pneumonia, patients with Crohn's disease, patients with ulcerative colitis. The effect of the cirrhosis and its medications spironolactone and rifaximin are compared to control groups.

Beta-blockers or Placebo for Primary Prophylaxis (BOPPP) of Oesophageal Varices Trial.

Research has proven that large varices can be treated with beta-blockers (a type of anti-hypertensive medication) to reduce the pressure in the veins. The management of small varices is still uncertain. This study aims to discover if beta blockers can be used in this setting. We hypothesize that beta blockers will reduce the risk of bleeding from small varices from 20% to 10% over a period of 3 years, resulting in significant cost savings to the NHS from better patient outcomes.

Erlotinib for Hepatocellular Carcinoma Chemoprevention

This phase II randomized placebo-controlled trial studies low-dose erlotinib treatment to assess its efficacy and safety to prevent development of hepatocellular carcinoma in patients with advanced liver fibrosis or cirrhosis.

SGLT-2 Inhibitors in the Treatment of Ascites

The goal of this observational study is to test the efficacy of glyphozines (SGLT-2 inhibitors) in the control of ascites in patients with liver cirrhosis in class A6-B9, according to the Child-Pugh classification, and type 2 diabetes mellitus. The investigators will compare patients belonging to the intervention group (A), who will be given SGLT-2 inhibitors according to diabetology indications in addition to standard medical therapy for 6, with patients of the control group (B), who will, instead, continue with the standard medical therapy for 6 months. Standard medical therapy will include dietary sodium restriction, treatment with diuretics (furosemide and spironolactone), hypoglycemic therapy (metformin, insulin, or both) and other supportive care. The main questions aims of this study are: 1. Compare the efficacy and safety of a therapeutic approach based on the administration of SGLT-2 inhibitors in addition to optimal medical therapy (MRA and loop diuretic) compared to traditional diuretic therapy only, in cirrhotic patients with saline retention and diabetes. 2. Demonstrate better control of the glycemic profile in cirrhotic diabetic patients using SGLT-2 inhibitors.

LiveSMART Trial to Prevent Falls in Patients With Cirrhosis - Supplementary Study

The LIVE-SMART supplementary study will assess social determinants of health (income, education, neighborhood deprivation), financial burden (out-of-pocket costs, productivity loss), financial distress (patient and caregiver-reported outcomes), and financial toxicity (healthcare utilization) among LIVE-SMART participants and their caregivers. Participants for this supplementary study are participants in the primary study (NCT05794555) and their caregivers.

Safety and Efficacy of Ketogenic Diet for Promoting Weight Loss in Obese Individuals With Compensated NASH Cirrhosis

This is an open-label, randomized study comparing a monitored ketogenic diet intervention using standard ketogenic diet (SKD) and standard of care (SOC) dietary recommendations for 16 weeks. Subjects enrolled in the standard of care group will receive a voucher to Weight Watchers after study completion.

CHronic Hepatopathies Associated With ALcohol Consumption aNd metAbolic Syndrome

The aim is to determine the metabolic factors, host immune factors, and medical imaging data associated with the development of HepatoCellular Carcinoma (HCC) in patients with alcohol-related liver disease or dysmetabolic steatosis/Non-Alcoholic SteatoHepatitis. The investigators will include patients with and without cirrhosis in order to identify early molecular mechanisms involved in the development of HCC especially in non-cirrhotic patients.

Prehabilitation for Patients Awaiting Liver Transplantation

This study will assess the feasibility, safety and effectiveness of a structured prehabilitation program combining exercise training, nutritional optimization and psychological support for patients with cirrhosis awaiting liver transplantation.

Development of 4D Flow MRI for Risk Stratification of Variceal Bleeding in Cirrhosis

The goal of this research is to validate novel non-invasive Magnetic resonance imaging (MRI) biomarkers to detect Gastroesophageal varices (GEV) in patients with cirrhosis, including fractional flow change in the portal vein and elevated azygos flow. End-stage liver disease (cirrhosis) is characterized by advanced fibrosis, liver failure, and portal hypertension. There are many causes of cirrhosis, including viral hepatitis, alcohol abuse, and perhaps most importantly, non-alcoholic fatty liver disease (NAFLD) and its aggressive subset, non-alcoholic steatohepatitis (NASH). 3 million new cases of end-stage liver disease (cirrhosis) are expected over the next decade. In cirrhosis, portosystemic collaterals that shunt blood away from the liver develop due to increased portal pressure. Gastroesophageal varices (GEV) are the most clinically relevant because they can cause fatal internal bleeding. GEV bleeding carries \~20% mortality at 6 weeks, and \~34% overall mortality. Identification of at-risk varices, prior to bleeding, is of paramount importance to initiate primary prophylaxis. To identify and treat at-risk patients, current guidelines recommend regular esophagogastroduodenoscopy (EGD) and variceal band ligation. Detection of high-risk GEV is key to initiating primary prophylaxis, which can reduce mortality by 50-70%. However, endoscopy is invasive and often unnecessary when no treatment is required. Therefore, the American Association for the Study of Liver Diseases has identified the development of "non-invasive markers that predict the presence of high-risk varices" as a major unmet need.

Online Prehabilitation for Patients Awaiting Liver Transplantation

Physical frailty is common in patients awaiting liver transplantation and has been associated with poor health outcomes. There is promising data from small studies showing that behavioural, nutrition, exercise therapy (prehabilitation) improves physical function in patients while they are waiting for a liver transplant. The proposed trial will assess if a 12-week online prehabilitation program improves physical function in patients listed for liver transplantation. Over 4 years, 177 patients will be recruited from 6 transplant centres across Canada and will be randomized to receive either the online prehabilitation program or usual care. The primary outcome of physical function will be evaluated using the FTSST at baseline and 12 weeks (or last timepoint before transplant) assessed virtually or in-person. Secondary outcomes include liver specific physical frailty, aerobic fitness, health-related quality of life (QoL), participant experience and acceptability. Exploratory outcomes include other virtual and in-person physical function measures, covert hepatic encephalopathy (CHE), sarcopenia, malnutrition, adherence, behaviour factors, clinical and post-transplant outcomes. Results will be compared between the intervention and usual care groups.

Effect of Fufang Biejiaruangan Combined With Antiviral Therapy on the Incidence of Hepatocellular Carcinoma in Patients With Hepatitis B-related Cirrhosis: A Multicenter, Randomized, Placebo-controlled Study

This study aims to establish a prospective, multicenter, randomized, double-blind, placebo-controlled parallel-group clinical trial cohort. The cohort will include high-risk populations for hepatitis B cirrhosis-related hepatocellular carcinoma (HCC) from multiple centers nationwide, who meet the criteria of traditional Chinese medicine syndrome differentiation as Qi-zhi-xue\_yu syndrome and have an aMAP score \>60 points. The objective is to evaluate whether combining Bie-jia-ruan-gan with standard anti-hepatitis B virus therapy can further reduce the incidence of HCC in this high-risk population.

Initial Resuscitation for Acute Kidney Injury in Cirrhosis

The goal of this interventional study is to evaluate two strategies for how to provide intravenous (IV) fluids for treating patients with acute kidney injury (AKI) in cirrhosis. The main question it aims to answer is: what is the safety, efficacy, and feasibility of providing a recommendation to use a Volume Assessment Guidance Algorithm (VAGA) or give standard of care doses of IV albumin? Patients will be randomly assigned where their treating teams will receive a VAGA-based recommendation or a standard of care IV albumin recommendation.

Transitional Care Program for Fluid Overload in Cirrhosis

The goal of this clinical trial is to learn about an intensive monitoring plan (transitional care program) in patients with cirrhosis and excessive swelling that are going to be discharged from the hospital. The main question\[s\] it aims to answer are: * How much time and what resources are needed to run such a program * How well do patients follow up with the phone calls, bloodwork, and doctor appointments? * Do the patients enrolled in the program have less need for hospitalization later, less kidney injury, better fluid control, and/or better survival compared to patients that are not in the program? Participants will * Be given a digital scale and a binder with educational material and a log to monitor their weights after discharge from the hospital * Receive a phone call from the study team within 72 hours of discharge and weekly * Be given a follow up appointment with hepatology within 4 weeks of discharge Researchers will compare participants in this program to patients that receive normal care to see if there are differences in need for hospitalization later, kidney injury, fluid control, and/or survival.

Liver Cancer Prevention Randomized Control Trial

To determine the effectiveness of a behaviorally-based tailored disease management intervention in patients with fibrosis or steatosis and risk factors for cirrhosis.

Changes in Bile Acids and Microbiota in Patients With Hepatitis D Treated With Bulvertide

HDV is an RNA virus that infects only in the presence of HBV, affecting about 13% of HBsAg carriers. In Italy, prevalence ranges from 3.2% to 9.3%. It increases the risk of cirrhosis, fulminant hepatitis, and HCC, particularly in high-risk groups (HIV, HCV, drug users, dialysis patients). Until 2020, pegIFN was the only therapy; since 2022, bulevirtide (BLV) has been available, blocking viral entry into hepatocytes and reducing HDV RNA and liver stiffness, with efficacy in 45-48% of patients, though the optimal treatment duration remains uncertain. The gut microbiota and bile acids also play a role in fibrosis and cirrhosis progression: dysbiosis, typical in cirrhotic patients, alters bile acid metabolism and increases intrahepatic toxicity.

Cirrhotic and Non-cirrhotic Patients With Clinically Significant Portal Hypertension

Alterations in conventional coagulation tests in patients with cirrhosis and/or portal hypertension do not reliably predict bleeding risk, as hemostatic balance is complex and often compensated. Many procedure-related bleeding events are driven by non-coagulatory factors, such as portal hypertension or technical aspects of the procedure. Most commonly performed procedures carry a low risk of bleeding even in the presence of elevated INR or thrombocytopenia, and no validated laboratory thresholds support prophylactic correction. Risk assessment should therefore be based on procedural factors, severity of liver disease, and systemic patient conditions, with correction of modifiable risk factors particularly before high-risk elective procedures.

ALTA TIPS: A 5-year Longitudinal Observational Study of Patients Undergoing TIPS Placement

ALTA is a multicenter consortium focused on the management of portal hypertension. ALTA TIPS is a longitudinal observational study of patients who are undergoing transjugular intrahepatic portosystemic shunt (TIPS) placement. ALTA will create a database that will provide clinical parameters and outcomes of patients undergoing TIPS as part of their standard of care in hopes of answering key clinical questions.

3D-MRE for Assessing Cirrhosis, Advanced Chronic Liver Disease and Portal Hypertension

How to construct a novel, non-invasive, accurate, and convenient method to achieve prediction of hepatic venous pressure gradient (HVPG) is an important general problem in the management of portal hypertension in cirrhosis or advanced chronic liver disease. We plan to investigate the ability of three demensional-magnetic resonance elastography (3D-MRE) to establish a risk stratification system and perform tailored management for portal hypertension in cirrhosis or advanced chronic liver disease.

RTX001 Autologous Engineered Macrophages for Liver Cirrhosis

The purpose of this study is to assess the safety and efficacy of RTX001 in patients with end-stage liver disease. This study is the first time RTX001, a macrophage cell therapy engineered to have an anti-inflammatory and anti-fibrotic effect, will be given to humans.